Antipsychotic drug treatment in first-episode psychosis: should patients be switched to a different antipsychotic drug after 2, 4, or 6 weeks of nonresponse?

Patients with schizophrenia show symptom reduction early after the initiation of drug treatment, but no consensus has been reached on the number of weeks after which a nonresponding patient should be switched to an alternative treatment. We aimed to test whether patients should be switched to an alternative treatment at 2, 4, or 6 weeks from treatment initiation. Remission within 12 months was assessed in 299 first-episode patients who completed the full 12-month European First-Episode Schizophrenia Trial. Logistic regression analyses were used to test whether the prediction of remission was improved by including assessments obtained 4 or 6 weeks from treatment initiation compared with a prediction based on baseline and 2-week measures only. Based on baseline and 2-week assessments, remission status was correctly predicted in 61% of the patients (positive and negative predictive power, 0.61 and 0.58, respectively; sensitivity, 0.94; and specificity, 0.12). This percentage increased to 63% (positive and negative predictive power, 0.67 and 0.55, respectively; sensitivity, 0.73; and specificity, 0.47) and 68% (positive and negative predictive power, 0.73 and 0.61, respectively; sensitivity, 0.73; and specificity, 0.60) by the inclusion of 4- and 6-week assessments, respectively. Although we confirmed earlier findings that 2-week measures of response are associated with remission, the prediction of remission is significantly improved by the inclusion of 4- and 6-week assessments. However, as the increase in prediction accuracy is modest, it is uncertain whether this improvement is clinically relevant.